Status: Finalised
First registered on:
24/02/2014
Last updated on:
21/03/2019
1. Study identification
EU PAS Register NumberEUPAS5896
Official titleRisk of Febrile Convulsions after 1st dose MMRV vaccination in comparison to MMR and MMR+V vaccination.
Study title acronymMMRV 1st dose
Study typeObservational study
Brief description of the studyIn July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a post-licensure study (Jacobsen et al., 2009) had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad® compared to separately administered MMR and V vaccines (MMR+V), a study investigating the risk of FC for Priorix-Tetra™ was requested by the Paul-Ehrlich Institute, the regulatory agency responsible for vaccine licensing and safety in Germany.
A retrospective matched cohort study was performed to provide risk estimates of FC after a first dose of Priorix-Tetra™ (MMRV) compared to MMR and MMR+V in pre-defined risk intervals. All children born between 01.01.2004 and 31.12.2008 who received a first dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V, respectively, by sex, age, month of vaccination and statutory health insurance provider.
The objective of this study was to estimate the risk of FC after a first dose vaccination with Priorix-Tetra™ compared to first dose vaccination with MMR or MMR+V vaccines in the pre-specified risk intervals: 0-4 days after immunization, 5-12 days after immunization (main risk interval), 13-30 days after immunization, and the entire risk period, that is 0-30 days after immunization.
Was this study requested by a regulator?Yes: Germany
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsBIPS GmbH
Department/Research groupClinical Epidemiology
Organisation/affiliationLeibniz Inst. for Prevention Research and Epidem.
Details of (Primary) lead investigator
Title Dr
Last name Schink
First name Tania
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
Germany
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed14/01/201114/01/2011
Start date of data collection01/01/200401/01/2004
Start date of data analysis14/01/201114/01/2011
Date of interim report, if expected
Date of final study report30/09/201114/03/2012
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesGlaxoSmithKline Biologicals SA100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Schink
First name Tania
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode28359
CountryGermany
Phone number (incl. country code)49-421-21856865
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Schink
First name Tania
Address line 1Achterstraße 30
Address line 2
Address line 3
CityBremen
Postcode28359
CountryGermany
Phone number (incl. country code)49-421-21856865
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)J07BD54 (measles, combinations with mumps, rubella and varicella, live attenuated)
7. Medical conditions to be studied
Medical condition(s)Yes
Febrile convulsion
8. Population under study
Age
Infants and toddlers (28 days - 23 months)
Children (2 - 11 years)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects286622
Additional information
82,656 (29%) children received the MMRV vaccine.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Administrative database, e.g. claims database
11. Scope of the study
What is the scope of the study?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
The objective of this study was to estimate the risk of febrile convulsions after a first dose vaccination with Priorix-Tetra® in comparison to first dose vaccination with MMR or MMR+V in the pre-specified risk intervals: 0-4 days after immunization, 5-12 days after immunization (main risk interval), 13-30 days after immunization, and the entire risk period, that is 0-30 days after immunization.
Are there primary outcomes?Yes
The primary outcome of this study was the occurrence of febrile convulsions (FC) defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis.
Are there secondary outcomes?Yes
The secondary outcome was defined as closely as possible to the outcome-criteria specified by the previous study by Jacobsen et al. That is, only hospitalizations for FC with a neurological condition coded as main discharge diagnosis were excluded.
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
A retrospective matched cohort study was performed to provide risk estimates of febrile convulsion after a first dose of Priorix-Tetra™ (MMRV) compared to MMR and MMR+V in pre-defined risk intervals according to the number of days after immunization (0-4, 5-12, 13-30, and the entire risk period (0-30)).
Children born between 01.01.2004 and 31.12.2008 who received a first dose of MMRV were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V, by sex, age, month of vaccination and health insurance provider.
Cumulative incidences (=risks) of primary and secondary outcomes with 95% CIs were calculated for all exposure groups within each risk interval. Risk ratios and risk differences of the primary and secondary outcomes were calculated with 95% CIs. Confounder adjusted odds ratios with corresponding 95% CIs were estimated to compare the MMRV exposure group with each of the comparison exposure groups using a separate binary logistic regression model for each risk interval.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Not submitted
18. Study Results
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Schink, T., et al. (2014). "Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination." Vaccine 32(6): 645-650.
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
